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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

F3/ contactin acts as a functional ligand for Notch during oligodendrocyte maturation.

Axon-derived molecules are temporally and spatially required as positive or negative signals to coordinate oligodendrocyte differentiation. Increasing evidence suggests that, in addition to the inhibitory Jagged1/Notch1 signaling cascade, other pathways act via Notch to mediate oligodendrocyte differentiation. The GPI- linked neural cell recognition molecule F3/ contactin is clustered during development at the paranodal region, a vital site for axoglial interaction. Here, we show that F3/ contactin acts as a functional ligand of Notch. This trans-extracellular interaction triggers gamma-secretase-dependent nuclear translocation of the Notch intracellular domain. F3/Notch signaling promotes oligodendrocyte precursor cell differentiation and upregulates the myelin-related protein MAG in OLN-93 cells. This can be blocked by dominant negative Notch1, Notch2, and two Deltex1 mutants lacking the RING-H2 finger motif, but not by dominant-negative RBP-J or Hes1 antisense oligonucleotides. Expression of constitutively active Notch1 or Notch2 does not upregulate MAG. Thus, F3/ contactin specifically initiates a Notch/Deltex1 signaling pathway that promotes oligodendrocyte maturation and myelination.[1]

References

  1. F3/contactin acts as a functional ligand for Notch during oligodendrocyte maturation. Hu, Q.D., Ang, B.T., Karsak, M., Hu, W.P., Cui, X.Y., Duka, T., Takeda, Y., Chia, W., Sankar, N., Ng, Y.K., Ling, E.A., Maciag, T., Small, D., Trifonova, R., Kopan, R., Okano, H., Nakafuku, M., Chiba, S., Hirai, H., Aster, J.C., Schachner, M., Pallen, C.J., Watanabe, K., Xiao, Z.C. Cell (2003) [Pubmed]
 
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